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Tuesday, 22 October 2013

New drug has potential to treat marijuana addiction

This is the original version of an article that was written by Matt Field and edited for The Conversation, you can find that version here.

More than 1.2 million Americans
per year seek treatment for problems with their marijuana (or cannabis) use.
Cannabis use disorder is recognised in the same category as other substance use
disorders (‘addictions’), in the Diagnostic and Statistical Manual
of Mental Disorders, and up to 1% of the European population may warrant
this diagnosis. Psychological treatments such as motivational interviewing and
cognitive behaviour therapy may be
effective, although there have been very few controlled trials of these
therapies. A recent review
concluded that there were no effective medications for the prevention of
relapse to cannabis use.

Like other
addictive drugs, Delta-9-tetrahydrocannabinol (THC; the main psychoactive
ingredient in cannabis), produces its rewarding effects by stimulating dopamine
release in the brain’s reward system, a network of brain structures including
the Nucleus Accumbens (NAcc) and the ventral tegmental area (VTA). Therefore, one potential way to treat
addictions would be to give medications that block dopamine activity in the
reward system, such as the dopamine antagonist drugs that are used to treat
schizophrenia. Unfortunately, these drugs have some unpleasant side-effects.
More fundamentally, dopamine antagonists block all forms of reward, not just
drug-induced reward. Therefore, the search is on for drugs that can interfere
with drug-induced reward without producing unpleasant side-effects, and without
interfering with the response to other rewards.

A
study recently published in Nature
Neuroscience has identified a promising potential new medication for
cannabis use disorders. The drug, RO 61-8048, leads to increases in levels of
kynurenic acid (KYNA). Through a fairly complicated mechanism, what this does
is block the ability of THC (and similar compounds) to increase dopamine
activity in the brain’s reward centre. Most importantly, although the drug can blunt
the effect of THC on dopamine levels, it has no effect on dopamine levels when
given on its own. In this paper, the authors conducted a series of studies with
rodents and primates, and they found that:

The drug prevented the increase
in dopamine levels in NAcc and the VTA that normally occurred after infusion of
THC.

The drug blocked the
reinforcing effects of THC: after receiving the drug, animals were less likely
to press a lever in order to obtain injections of THC or a related compound.

The drug could block the
rewarding effects of THC. For example, animals will normally press a lever to
receive THC if they have just been given an injection of THC or if they have
been presented with environmental signals that THC was available (these tests
are considered animal models of relapse to drug use). The drug reduced both of
these effects.

These effects of the drug were
specific to THC, because the drug did not affect the reinforcing properties of another
reward: food. Animals were prepared to press a lever in order to win food
pellets, regardless of whether they had received the drug or not.

At the doses studied, the drug
had no effect on working memory, and did not change the memory-impairing
effects of THC.

These findings are
potentially important because has been very difficult to develop medications
that block drug-induced reward without also interfering with the response to
other rewards. The safety of the drug, and its effectiveness as a treatment for
cannabis use disorders, should now be studied in human volunteers.

We should be
cautious, however. Even if the drug is safe in humans, and it can reduce the
rewarding effects of cannabis, this will not make it a panacea for cannabis use
disorders. Medications for other substance use disorders, such as naltrexone for
alcohol use disorders and buprenorphine
for opiate use disorders are prescribed because they reduce the rewarding
effects of alcohol or heroin if those drugs are consumed. Although the drugs
are effective, if a patient decides that they want to experience the rewarding
effects of alcohol or heroin again, all they have to do is stop taking their
medication. This is also likely to be the case for RO 61-8048 and cannabis use
disorders. Medication implants and depot formulations may
partly solve this problem.